- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Baer, M., Zhong, Y., Yu, B., Tian, T., He, X., Gu, L., Huang, X., Gallina, E., Metzen, I. E., Bucher, M., Song, R., Gutjahr, C., SU, Z., Moya, Y., von Wiren, N., Zhang, L., Yuan, L., Shi, Y., Wang, S., Qi, W., Baer, M., Zhao, Z., Li, C., Li, X., Hochholdinger, F., Yu, P.Efficient nutrient use in agriculture depends on the dynamic interplay between plant roots, soil, and microbial communities. The roo rhizosphere interface is central to nutrient uptake and serves as a key hub for interactions with beneficial microbes. Arbuscular mycorrhizal (AM) fungi, positioned at the nexus between plant roots and soil microbiota, play a critical role in enhancing crop performance under nutrient-limited conditions. In this study, we dissected the genetic and molecular basis of AM fungi induced lateral root development in […]
- by Juneja, P., Sharma, A., SHarma, B., KUMAR, G., Jakhar, D., Chauhan, N., Khillan, V., Mukund, A., Tripathi, D. M., Sarin, S. K., Maiwall, R., Kaur, S.Background and Objective: Mesenteric lymph nodes (MLN) are immunological barriers against bacterial translocation (BT). Enhanced gut BT through MLN facilitates bacterial spread and higher mortality in cirrhosis. We aimed to elucidate mechanisms underlying MLN failure to effectively contain BT during advanced cirrhosis. Design: BT and immune cells were analyzed in lymphoid organs and circulation of control and CCl4 models, with and without MLN (MLNx). MLN proteomics identified versican (VCAN) as major upregulated protein in cirrhosis, whose immunomodulatory function was examined […]
- by Tsang, Y. P., Wang, K., Kelly, E. J., Mao, Q., Unadkat, J. D.Introduction Infection and inflammation elevate circulating pro-inflammatory cytokines that can affect renal drug clearance. Accordingly, we sought to (i) quantify the extent of modulation of renal drug-metabolizing enzymes and transporters (DMETs) by cytokines and (ii) identify the mechanism(s) underlying these effects. Methods Fresh primary human proximal tubular epithelial cells (PTECs) were cultured on extracellular matrix-coated Transwells. PTECs were exposed every 24 h, for 48 h, to IL-6, IL-1{beta}, TNF-, IFN-{gamma}, IL-4, or IL-10 (0.1 or 1 ng/mL), individually or as […]
- by Sun, R., Yang, P., Wang, L., Hu, Y., Yang, Y., Deng, F., Li, S., Fan, M., Xia, X., Li, Y.Distinguishing among neuronal cell types is crucial for deciphering complex neural networks and brain functions. However, the current repertoire of cell-labeling tools compatible with light microscopy (LM) and/or electron microscopy (EM) is limited compared to the vast number of cell types in the brain. Here, we introduce PKU (polymer king-size unit) tags, genetically encoded shape tags that leverage the polymerization of self-assembling proteins, spectrally distinct fluorescent proteins and, optionally, a nuclear targeting sequence to generate a series of multi-shaped (spherical […]
- by Sturm, K., Pri-Tal, O., Rico-Resendiz, F., Verma, Y., Richter, A., Chen, H., Broger, L., Hothorn, L. A., Fiedler, D., Panse, V. G., Hothorn, M.Inositol pyrophosphates (PP-InsPs) are key nutrient messengers in plants, but their protein receptors remain poorly defined. Using a systems-level affinity screen with biotinylated InsP, InsP, and InsP in Arabidopsis thaliana, we identify multiple conserved PP-InsP-interacting complexes involved in mRNA metabolism, translation, and cell signaling, including the nuclear -subunits of casein kinase II (CK2). The CK2 subunit AtCKA1 associates with the PP-InsP kinase AtVIH2, and its 1.9 [A] crystal structure with InsP6 reveals two conserved PP-InsP binding sites located in the […]
- by Montesinos, J., Yun, T., Salomon-Cruz, I. D., Agudelo-castrillon, S., Uceda, M., Ferrer, A. C., Anton-Barros, C., Gomez-lopez, N., Agrawal, R. R., Larrea, D., Velasco, K. R., Fernandez-Bernal, A., Benitez, E., Zhu, X., Schon, E. A., Cardona-Gomez, G. P., Area-Gomez, E.The structure and function of cellular and intracellular membranes are critically governed by the fatty acid (FA) composition of phospholipids (PLs), which is dynamically regulated by a network of enzymes that fine-tune lipid species according to cellular demands. In this study, we identify a mechanism through which the formation of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) modulates the activity of the acyl-CoA synthetase long-chain family member 4 (ACSL4), an enzyme that channels polyunsaturated fatty acids (PUFAs) into phosphatidylcholine (PC) via […]
- by Dinter, T., Mackowiak, S., Rogers, Z., Bhandarkar, V., Carney, M., Zhang, Y., Morgan, D., Pop, L., Chatterjee, F., Lutz, E., Jain, Y., Radhakrishnan, A., Lander, E., Wittrup, K., Love, J. C., Meissner, A., Spranger, S.In cancer, CD8+ T cell responses are dominated by exhausted T cells, which can be reinvigorated using immune checkpoint blockade therapy and can control large tumors. However, it remains unclear which T cell fate best supports long-term immunity following tumor regression or clearance and a period of minimal antigen load. This question is particularly relevant following surgical tumor resection, when tuning the immune system could prevent recurrence. To determine which T cell fate provides durable protection following surgery and metastatic […]
- by Yan, J., Cai, J., Li, Y., Lin, Z., Xian, W., Wei, X., Lei, I. F., Zhou, M., Campbell-Valois, F.-X., Siu, S. W. I.Antimicrobial peptides (AMPs) represent a promising therapeutic strategy to combat the increasing challenge of multidrug-resistant pathogens, a crisis intensified by the overuse of conventional antibiotics. In addition to their broad-spectrum antimicrobial activity, low toxicity, and reduced propensity for resistance development, AMPs offer significant advantages over traditional antibiotic therapies. However, the discovery of novel AMPs through biological experiments remains constrained by high costs, labor-intensive workflows, and time-consuming procedures, underscoring the urgent need for in silico computational methods to design AMP sequences. […]
- by Gong, K., Lu, T., Wang, X., Liu, X.Cytotoxic chemotherapy and immune checkpoint inhibitors (ICIs) have transformed the management of advanced cancers, yet durable responses remain restricted to subsets of patients and strongly depend on the tumor immune microenvironment (TIME). Distinct hot and cold TIMEs differ in pre-existing effector T-cell activity and treatment-induced immunogenicity, suggesting that combination regimens should be tailored to microenvironmental context under realistic clinical constraints. Here we develop a deterministic dynamic optimization framework that jointly designs chemotherapy and ICI dosing schedules on a mechanistic tumor-immune […]
- by Rudnizky, S., Murray, P. J., Sorensen, E. W., Koenig, T. J. R., Pangeni, S., Merino-Urteaga, R., Chhabra, H., Caccianini, L., Davidson, I. F., Osorio-Valeriano, M., Hook, P. W., Meneses, P., Hao, J., Zarb, J. S., Hatzakis, N. S., Timp, W., Farnung, L., Vos, S. M., Peters, J.-M., Aksimentiev, A., Ha, T.CCCTC-binding transcription factor (CTCF) and the cohesin complex shape the genome into loops and topologically associating domains (TADs), yet the mechanisms linking CTCF dynamic behavior to its function as a cohesin barrier remain unclear. Using integrated experimental and computational approaches, we demonstrate that individual CTCF-DNA complexes are intrinsically mobile over distances and timescales compatible with cohesin capture during loop extrusion, driven by the dynamic rearrangements of zinc finger (ZF) domains. Genome-wide single-molecule accessibility and sequencing analyses further reveal that these […]
- by Rout-Pitt, N., Barnes, S., Reyne, N., McCarron, A., Donnelley, M., Kostecki, R., Noschka, E.We have developed a novel biosensing device that can detect the real-time, dynamic state of in vivo oxidative status (IVOS) in living systems. Oxidative stress is a well-established condition in CF animal models and humans. Elevated oxidative stress conditions are associated with excessive inflammatory responses from neutrophils that result in fibrotic tissue formation. As such, numerous clinical and preclinical studies suggest that elevated oxidative stress, combined with the heightened pro-inflammatory milieu observed in CF phenotypes, likely increases susceptibility to recurrent […]
- by Claire, S., Moreau, B., Boujard, M., Eric, G., Jouneau, P.-H., Barnes, J.-P.Time-of-flight secondary ion mass spectrometry (ToF-SIMS) enables label-free molecular imaging at submicrometric resolution, but its application to biological samples remains limited due to sample preparation challenges. Conventional fixation or dehydration alters morphology and induces analyte relocation, while cryo-transfer systems are costly and technically demanding. We present an in situ cryo-etching approach using a gas cluster ion beam (GCIB) and a new sample holder with a flat titanium ridge mask, enabling the sectioning of frozen specimens directly inside the ToF-SIMS instrument. […]
- by ANGULO, J., Uwizeye, C., Albanese, P., Menneteau, M., Ravanel, S., Jouneau, P.-H., Finazzi, G., Courtois, F.Iron is naturally present at low levels in modern oceans, but it remains essential for marine life. Ocean-dwelling organisms such as oceanic phytoplankton must therefore adapt to the available levels. Among phytoplankton, diatoms are a highly diverse and successful taxon that includes the Thalassiosira genus. As a group, diatoms contribute around 20% of global primary photosynthetic productivity, they have also developed specific resources allowing them to thrive in low-iron regions. However, the major biological factors underlying their success in these […]
- by Hadlik, M., Baranek, M., Barankova, K., Kovacova, V.Downy mildew, caused by Plasmopara viticola, is a major threat to grapevine. To investigate how pyramiding resistance loci influences early immune processes, we generated 36 time-resolved transcriptomes (0, 6, 24 hpi) from genotypes carrying single (Rpv12), double (Rpv12+1), or triple (Rpv12+1+3) resistance loci, together with a susceptible control. Aggregated expression divergence revealed that multilocus genotypes showed detectable baseline transcriptional differences prior to infection and distinct temporal trajectories following inoculation. Co-expression analysis identified five higher-order metamodules and uncovered non-additive network restructuring, […]
- by Li, Y., Zhu, J., Xu, P., Guo, M., Li, Y., Liu, H.Fluorescence microscopy plays a critical role in live-cell imaging, yet the captured images often suffer from significant noise due to limited excitation intensity and constrained exposure times. Deep learning has emerged as a powerful solution for image denoising, especially the self-supervised methods can achieve good restoration performance without requiring clean target data. However, their performance in preserving fine image details remains challenging under low signal-to-noise ratio (SNR) conditions. In this work, we propose a novel self-supervised denoising framework named Self-Supervised […]
- by Sun, J., Liang, C., Wei, R., Zheng, P., Yan, H., Bai, L., Zhang, K., Ouyang, W., Ye, P.Understanding cellular states urgently requires methods capable of integrating large-scale, heterogeneous single-cell and spatial omics data. However, these data are often completely unpaired due to destructive assays and suffer from technical noise, variable feature coverage, and immense scale. We present scMRDR, a scalable computational framework leveraging regularized disentangled representation learning to integrate multiple, completely unpaired single-cell omics datasets with heterogeneous resolutions and coverages. scMRDR overcomes common data-pairing requirements and computational bottlenecks by learning a unified, structure-preserving latent embedding, efficiently scalable […]
- by Espadas, J., Souza, D. P., Hakala, M., Garcia-Arcos, J. M., Tran, J., Kumar, A., Marcuello, C., Merino, A., Colom, A., Vanni, S., Kaksonen, M., Baum, B., Toret, C. P., Roux, A.The emergence of cell compartmentalization depends on membrane fission to create the endomembrane compartments. In eukaryotes, membrane fission is commonly executed by ESCRT-III, a protein complex conserved in all domains of life. However, whether membrane fission was an ancestral ESCRT-III activity predating eukaryogenesis remains unknown. Here we show that ESCRT-IIIA from Asgard Heimdallarchaeota, the closest archaeal relatives of eukaryotes, performs membrane fission through an N-terminal amphipathic helix, which we term Hofund. In eukaryotes, Hofund is fragmented across ESCRT-IIIA paralogs, and […]
- by Guo, Y., Zhang, Y., Li, X., Kuang, J., Cao, K., Chen, F., Fan, C., Zhao, Y.Recent years have witnessed profound advances in spatial transcriptomics (ST). However, current ST strategies are limited to tissue sections, unable to directly profile spatiotemporal transcriptome landscapes of individual living animals. To overcome this limitation, we present acupuncture-extracted in vivo spatiotemporal transcriptomics (aivST). It is mainly based on engineering clinical-grade acupuncture gold microneedles as a spatial-barcoding array patch with high-performance DNA recognition interfaces. These interfaces first utilize nanoparticles surface deposition to increase the density of DNA probes. A freeze-thawing method is […]
- by Luciano, P., Park, K., Audebert, S., Camoin, L., Nino, C. A., Park, D. K., Maudlin, I. E., Dubarry, M., lee, l., Oeffinger, M., Beggs, J. D., Kim, Y. H., Kim, J., Dichtl, B., Geli, V.Set1 is the catalytic subunit of SET1C or COMPASS, which methylates histone H3K4 and serves as a scaffold for the association of seven tightly bound polypeptides. We have employed yeast two-hybrid screenings to determine the interactome of Set1 and each subunit, providing a unique resource for exploring known and novel roles of the complex. Our screenings identified a multitude of interactors involved in chromatin regulation, DNA replication, meiotic breaks, and Ty transposition, processes previously associated with SET1C. Consistent with Set1 […]
- by Kinoshita, S., Sakurai, K., Tsusaka, T., Sakurai, M., Shirasawa, K., Isobe, S., Iwata, H.Despite their substantial therapeutic value, medicinal plants have undergone limited genetic improvement through breeding because of the scarcity of expert breeders. Moreover, quantifying bioactive compounds is expensive. Genomic selection (GS), which leverages genome-wide markers to predict breeding values and assemble favorable alleles, offers a practical way to unlock latent genetic potential. As a model case, we evaluated GS in red perilla (Perilla frutescens). Building on previous work, we implemented a cross-selection strategy that prioritized segregation variance by selecting crosses based […]